PURPOSE: Solid tumors exhibit an altered redox state in comparison with normal tissues due to tumor hypoxia, lower pH, and elevated levels of the tripeptide glutathione. This study describes the preparation of functional redox-responsive nanoparticles proposed as delivery vehicle of Doxorubicin in adrenocortical cancer in vitro. METHODS: Curcumin and Lipoic acid were conjugated to Human Serum Albumin and nanoparticle systems were prepared via a modified desolvation method. Scanning electron microscopy, Fourier transmission IR, dynamic light scattering and differential scanning calorimetry analyses were used to characterize the nanoparticles. Balb3T3 and H295R were used as in vitro models of health and cancer cells, respectively. RESULTS: Nanoparticles with a spherical shape and a mean diameter of 70 nm were observed, increasing up to ten-folds upon exposure to glutathione 10 mM. Redox responsive Doxorubicin release was recorded, with loaded nanoparticles significantly enhancing the drug cytotoxicity against H295R adrenocortical tumor cells. Cell uptake experiments revealed a rapid and efficient internalization of the nanoparticles. CONCLUSIONS: A valuable tools to actively improve the in vitro anticancer activity of Doxorubicin against adrenocortical cancer was proposed. The effectiveness of the delivery vehicle is related to the presence of both Lipoic acid and Curcumin moieties, enhancing the glutathione responsivity, and the drug cytotoxicity, respectively.

Functional Albumin Nanoformulations to Fight Adrenocortical Carcinoma: a Redox-Responsive Approach

Curcio M.
;
Avena P.;Cirillo G.;Casaburi I.;Spizzirri U. G.;Nicoletta F. P.;Iemma F.;Pezzi V.
2020

Abstract

PURPOSE: Solid tumors exhibit an altered redox state in comparison with normal tissues due to tumor hypoxia, lower pH, and elevated levels of the tripeptide glutathione. This study describes the preparation of functional redox-responsive nanoparticles proposed as delivery vehicle of Doxorubicin in adrenocortical cancer in vitro. METHODS: Curcumin and Lipoic acid were conjugated to Human Serum Albumin and nanoparticle systems were prepared via a modified desolvation method. Scanning electron microscopy, Fourier transmission IR, dynamic light scattering and differential scanning calorimetry analyses were used to characterize the nanoparticles. Balb3T3 and H295R were used as in vitro models of health and cancer cells, respectively. RESULTS: Nanoparticles with a spherical shape and a mean diameter of 70 nm were observed, increasing up to ten-folds upon exposure to glutathione 10 mM. Redox responsive Doxorubicin release was recorded, with loaded nanoparticles significantly enhancing the drug cytotoxicity against H295R adrenocortical tumor cells. Cell uptake experiments revealed a rapid and efficient internalization of the nanoparticles. CONCLUSIONS: A valuable tools to actively improve the in vitro anticancer activity of Doxorubicin against adrenocortical cancer was proposed. The effectiveness of the delivery vehicle is related to the presence of both Lipoic acid and Curcumin moieties, enhancing the glutathione responsivity, and the drug cytotoxicity, respectively.
adrenocortical carcinoma; curcumin conjugate; human serum albumin nanoparticles; redox-responsive
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/298893
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